Autophagy Signaling in Prostate Cancer: Identification of a Novel Phosphatase
Abstract
Phosphatidylinositol-3-phosphate (PI(3)P) is concentrated on autophagic vesicles and recruits effector proteins critical for this process. The production of PI(3)P by the class III phosphatidylinositol 3-kinase (PI3K), Vps34, has been well established; however, phosphatases which antagonize this early step in autophagy are not clear. To identify such enzymes, we screened human phosphatase genes by RNA interference (RNAi) and found that loss of PTPsigma, a dual-domain protein tyrosine phosphatase (PTP), increases cellular PI(3)P. Accordingly, we discovered that loss of PTPsigma hyperactivates both constitutive and induced autophagy. Finally, we found that PTPsigma localizes to PI(3)P-positive membranes in cells and this vesicular localization is enhanced during autophagy. Our findings propose a novel role for PTPsigma and provide insight into the regulation of autophagy. Mechanistic knowledge of this process is critical for understanding and targeting therapies for several human diseases, including prostate cancer, in which abnormal autophagy may be pathological.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA549765
Entities
People
- Jeffrey P. Mackeigan